This proposal is for the study of the renal disposition of drugs. The actions of drugs on the kidney, and drug interactions. The subprojects are: 1) A study of the active reabsorptive mechanism(s) for drugs. The questions addressed are: Can mutual inhibition of transport be demonstrated among the various drugs which are actively reabsorbed? Is this reabsorptive mechanism the same as the mechanism for uric acid? Can active reabsorptive fluxes be demonstrated for uricosuric drugs which do not seem to be reabsorbed in clearance experiments? 2) The uricosuric action of zoxazolamine. The question is: Can an organic base per se be uricosuric or must it be converted in vivo to an anionic metabolite. 3) The hypocalicuric action of chlorothiazide. The question: Is the hypocalcuric action a result of inhibition of the enzyme(s) phosphodiesterase? 4) A macromolecular inhibitor of carbonic anhydrase. The question: What is the quantitative role of lumenal carbonic anhydrase in the reabsorption of bicarbonate? The experiments will be conducted in dogs, chimpanzees, Cebus monkeys and rats. The major techniques are renal clearance, stop-flow, micropuncture, microperfusion.